There is a significant medical need for an adhesive that can bond strongly to soft tissues and incisions that facilitates healing and minimizes inflammation. These materials can potentially reduce operating time, tissue handling, and mitigate complications such as infection. While numerous tissue adhesives exist, their applications are restricted due to limitations such as insufficient mechanical properties, increased inflammation and difficulty in application to certain wound geometries. We have recently developed a textured tissue tape that is biocompatible with tunable mechanical, degradation and adhesive properties. Functional testing against tissue showed maximum adhesion strength of 0.8 N/cm2, but in order to translate these materials to medical applications, adhesion strengths of ~5-15 N/cm2 are required. In this proposal, we aim to develop an adhesive that bonds strongly and can be applied to a variety of tissues. We will reveal the fundamental scientific and engineering principles required to fabricate biologically interfacing adhesives with well-defined surface morphologies and chemistries without inducing a significant inflammatory response. Through enhancing the adhesion of our existing nanostructured tapes and through elucidating mechanisms that impact adhesion to different tissues, the proposed research will provide a potential platform for discovery of new science that leads to many practical and useful additions to the surgical armentarium. Specifically, a new class of strongly adhesive micro/nano textured biomaterials will be developed by controlling the surface features of biocompatible polymers on the micro and nanoscale, and by systematically developing an understanding of how topography, porosity, and chemistry influence adhesion to biological tissues. Through using soft, flexible materials, the textured surfaces should easily conform to irregularly shaped surfaces, such as soft tissue, thereby maximizing molecular interactions at the interface.